Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis

Our plain-English summary of Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis, by T. Berghmans, M. Paesmans, Y. Lalami, et al (Lung Cancer, 2002).

The study

• Authors: T. Berghmans, M. Paesmans, Y. Lalami, I. Louviaux, S. Luce, C. Mascaux, A.P. Meert, J.P. Sculier
• Journal: Lung Cancer
• Published: 2002;38(2):111-21
• Type of article: Meta-analysis, Systematic review
• Cited by: 132 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.

Copyright 2002 Elsevier Science Ireland Ltd.

In plain English

This systematic review with meta-analysis covered chemotherapy and immunotherapy trials in pleural or peritoneal malignant mesothelioma, not asbestos exposure. It included 83 articles from 1983 to June 2001, covering 88 treatment arms and 2320 patients assessable for tumor response. The authors scored trial reporting quality and pooled response rates in four groups. Regimens with both cisplatin and doxorubicin had the highest response rate, 28.5% (43 of 151; 95% CI 21.3 to 35.7%). Cisplatin without doxorubicin gave 23.2% (127 of 547; 95% CI 19.7 to 26.8%), not a statistically significant difference (P = 0.22). Doxorubicin without cisplatin (11.3%, 24 of 213; CI 7.0 to 15.5%) and regimens with neither (11.6%, 164 of 1409; CI 10.0 to 13.3%) did not differ. Cisplatin regimens had higher response rates than carboplatin regimens (24.0%, 170 of 698, versus 11.6%, 13 of 112; P = 0.004). The authors called these non-randomised comparisons exploratory. They concluded that, by objective response rate, cisplatin plus doxorubicin was the most active regimen and cisplatin the best single agent. They recommended the combination as the reference arm for future trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review of published prospective treatment trials, with quality scoring and pooled (meta-analysis) comparison of response rates
• Who was studied: 83 published articles on malignant mesothelioma (pleural or peritoneal), published 1983 to June 2001 (literature searched from 1965). These gave 88 treatment arms: 80 single-arm phase II trials, 3 randomised phase II trials, and two papers that each reported two trials. In total, 2320 patients were assessable for response
• Exposure: No asbestos exposure was studied. The review compared chemotherapy and immunotherapy regimens, grouped by whether they contained cisplatin, doxorubicin, both, or neither
• Main results:
  • Of the 88 trial arms, 35 were classed as negative, 5 as positive and 48 as potentially positive for tumor response
  • Reporting-quality scores did not differ significantly between positive and negative trials (median global score 57.2% versus 54.1%)
  • Response rates differed significantly across the four regimen groups (P less than 0.001)
  • Group 3 (cisplatin and doxorubicin) had a response rate of 28.5% (43 of 151, 95% CI 21.3 to 35.7%). Group 1 (cisplatin without doxorubicin) had 23.2% (127 of 547, 95% CI 19.7 to 26.8%). The P value for this comparison was 0.22
  • Group 2 (doxorubicin without cisplatin) had 11.3% (24 of 213, 95% CI 7.0 to 15.5%). Group 4 (neither drug) had 11.6% (164 of 1409, 95% CI 10.0 to 13.3%). These two groups did not differ (P = 0.97)
  • Cisplatin-containing regimens had a higher response rate than carboplatin-containing regimens (24.0%, 170 of 698, versus 11.6%, 13 of 112; P = 0.004)
  • Combination regimens had a higher response rate than single-agent regimens (22.6%, 184 of 815, versus 11.6%, 174 of 1505; P less than 0.001). The authors noted that most single-agent trials were in Group 4
  • Once cisplatin-containing studies were removed, doxorubicin and epirubicin no longer differed significantly (11.3%, 24 of 213, versus 9.1%, 10 of 110; P = 0.70)
  • Response rates were higher in studies using CT scan to assess response (20.0%) than in studies using standard X-ray (3.4%) or not stating the method (10.3%)
• The authors' conclusion: The authors concluded that, in terms of objective tumor response rate, cisplatin plus doxorubicin was the most active regimen and cisplatin the best single agent. They recommended the combination as the reference arm for future randomised phase II or III trials
• Limitations the authors state:
  • The pooled comparisons are open to bias from differences in quality and methodology between trials, including patient selection
  • The comparisons were not protected by randomisation
  • The results can only be considered exploratory
  • Statistical methods were often poorly described, so some negative trials may have lacked power and been wrongly interpreted as negative
  • Tumor response in mesothelioma is hard to measure
  • Survival and toxicity data were too poorly reported to pool
  • Immunotherapy trials were too varied for meaningful conclusions

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Immunotherapy, Malignant Mesothelioma, Systematic Review, Meta-Analysis, Unresectable, Lung Cancer, confidence interval.

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